Effects of Hyperferritinemia on Functional Outcome in Acute Ischemic Stroke Patients with Admission Hyperglycemia

Qian, Wei; Wei, Chuanliang; Wang, Yanan; Liu, Junfeng

doi:10.1159/000527860

Cited by 2 publications

(2 citation statements)

References 35 publications

(67 reference statements)

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“…However, the relationship did not exist after adjusting confounders in all patients with IS. 35 A study proceeding from a 6-month follow-up has also indicated a similar conclusion. 36 However, contrasting results have been reported.…”

Section: Discussionmentioning

confidence: 66%

Causal Association of Iron Status With Functional Outcome After Ischemic Stroke

He,

Wang,

et al. 2024

Stroke

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BACKGROUND: Iron status has been associated with functional outcomes after ischemic stroke (IS). Nonetheless, this association may be affected by confounders. We perform Mendelian randomization to clarify the causal association between iron status and functional outcome after IS. METHODS: We obtained summary-level statistics related to iron status biomarkers from a meta-analysis of a gene-wide association study conducted by the Genetics of Iron Status Consortium, which included 11 discovery cohorts and 8 replication cohorts. We also took genetic variants related to 4 biomarkers of iron status from combining gene-wide association study results of Iceland, the United Kingdom, and Denmark to perform a replicate Mendelian randomization analysis. This data set included 4 iron status biomarkers, namely, ferritin, total iron binding capacity, iron, and transferrin saturation (TSAT). The confounders in these data sets have been adjusted to mitigate the collider bias. We acquired summary statistics data sets for functional outcomes following IS from the gene-wide association study meta-analysis conducted by the Genetics of Ischemic Stroke Functional Outcome Consortium. The genetic estimates for functional outcomes at 90 days after IS were evaluated by the modified Rankin Scale score, including 3741 cases with good functional outcomes (modified Rankin Scale score, 0–2) and 2280 subjects with poor functional outcomes post-stroke (modified Rankin Scale score, 3–6). Inverse variance weighting was used as the primary method, complemented by sensitivity analyses for pleiotropy and increasing robustness. RESULTS: Reported with odds ratios (ORs) of stroke outcome with per SD unit increase in genetically determined iron status biomarker, TSAT and iron were associated with poor functional outcome after IS (TSAT: OR, 1.36 [95% CI, 1.23–1.50]; P =2.27×10 − 9 ; iron: OR, 1.44 [95% CI, 1.13–1.85]; P =0.0033). In replicate Mendelian randomization analysis, the detrimental effects of iron on poor functional outcome after IS remained stable (OR, 1.60 [95% CI, 1.24–2.08]; P =0.0003). In the meta-analysis, iron and TSAT were associated with poor functional outcomes after IS (TSAT: OR meta , 1.35 [95% CI, 1.23–1.48]; iron: OR meta , 1.51 [95% CI, 1.27–1.81]). Through sensitivity analyses and reverse Mendelian randomization analyses, we confirmed the robustness of the results. CONCLUSIONS: Our study provides evidence suggesting a potential causal relationship between iron status and poor functional outcomes after IS. Future studies are required to illuminate the underlying mechanism.

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Section: Discussionmentioning

confidence: 66%

Causal Association of Iron Status With Functional Outcome After Ischemic Stroke

He,

Wang,

et al. 2024

Stroke

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“…23 However, recently it has been shown that hyperferritinemia is associated with poor functional outcomes only in hyperglycemic patients, which might suggest that factors related to oxidative stress might play an additional role in the mechanism of brain damage in acute ischemia. 24 Transferrin binds free iron, acting as a free radical scavenger and is downregulated during inflammation. Higher levels of transferrin decrease the risk of stroke, 25 correlate inversely with clinical status, and may be protective against early deterioration.…”

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confidence: 99%

Protein Carbonylation Contributes to Prothrombotic Fibrin Clot Phenotype in Acute Ischemic Stroke: Clinical Associations

Błaż,

Natorska,

Bembenek

et al. 2023

Stroke

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BACKGROUND: Acute ischemic stroke (AIS) is associated with enhanced oxidative stress and unfavorably altered fibrin clot properties. We investigated determinants of plasma protein carbonylation (PC) in AIS, its impact on the prothrombotic state, and prognostic value during follow-up. METHODS: We included 98 consecutive AIS patients aged 74±12 years (male:female ratio, 50:48 [51%:49%]) at the Neurology Center in Warsaw, Poland, between January and December 2014. As many as 74 (75.5%) patients underwent thrombolysis, and 24 were unsuitable for thrombolysis. We determined plasma PC, along with thrombin generation, fibrin clot permeability, and clot lysis time on admission, at 24 hours, and 3 months. Stroke severity was assessed using the National Institutes of Health Stroke Scale and stroke outcome with the modified Rankin Scale. Hemorrhagic transformation was assessed on the computed tomography scan within 48 hours from the symptom onset, while stroke-related mortality was evaluated at 3 months. RESULTS: On admission, PC levels (median, 4.61 [3.81–5.70] nM/mg protein) were associated with the time since symptom onset (r=0.41; P <0.0001) and with the National Institutes of Health Stroke Scale score ( P =0.36; P =0.0003). Higher PC levels on admission correlated with denser fibrin clot formation and prolonged clot lysis time but not with thrombin generation. In thrombolysed patients, lower PC levels were observed after 24 hours (−34%) and at 3 months (−23%; both P <0.001). PC levels at baseline and after 24 hours predicted the modified Rankin Scale score >2 at 3 months (OR, 1.90 [95% CI, 1.21–3.00]; OR, 2.19 [95% CI, 1.39–3.44], respectively). Higher PC at baseline predicted hemorrhagic transformation of stroke (OR, 1.95 [95% CI, 1.02–3.74]) and stroke-related mortality (OR, 2.02 [95% CI, 1.08–3.79]), while higher PC at 24 hours predicted solely stroke-related mortality (OR, 2.11 [95% CI, 1.28–3.46]). CONCLUSIONS: Elevated plasma PC levels in patients with AIS, related to prothrombotic fibrin clot properties, are associated with stroke severity. Thrombolysis reduces the extent of PC. The current study suggests a prognostic value of PC in AIS.

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Effects of Hyperferritinemia on Functional Outcome in Acute Ischemic Stroke Patients with Admission Hyperglycemia

Cited by 2 publications

References 35 publications

Causal Association of Iron Status With Functional Outcome After Ischemic Stroke

Causal Association of Iron Status With Functional Outcome After Ischemic Stroke

Protein Carbonylation Contributes to Prothrombotic Fibrin Clot Phenotype in Acute Ischemic Stroke: Clinical Associations

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